Discorea nipponica saponins restore the Th17/Treg balance in aplastic anemia through the Notch/RBPJκ/FOXP3/RORγt axis
Discorea nipponica saponins restore the Th17/Treg balance in aplastic anemia through the Notch/RBPJκ/FOXP3/RORγt axis
复制标题
日本铁盘皂苷通过 Notch/RBPJ kappa/FOXP3/ROR gamma t 轴恢复再生障碍性贫血中 Th17/Treg 平衡
DOI：
10.1016/j.jksus.2019.12.026
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发表时间：
2020-03-01
影响因子：
3.8
通讯作者：
Liu, Baoshan
中科院分区：
文献类型：
--
作者：
Song, Xinlong;Zhang, Le;Liu, Baoshan
T细胞分化是再生障碍性贫血（AA）的一个重要病理过程。Tregs和Th17必须保持平衡才能产生有效的免疫耐受。disrea nipponica皂苷（DNS）通过增加辅助性t细胞的数量，同时降低t细胞毒性细胞的百分比，促进AA模型造血后的恢复。然而，DNS导致这些治疗效果的机制在很大程度上仍未明确。在这里，我们探讨了DNS在小鼠AA模型中调节T细胞亚群的机制。采用Cs-137照射和腹腔注射环磷酰胺和氯霉素建立BALB/c雄性小鼠AA模型。小鼠每天灌胃给药DNS/雷公藤多苷片(TW)/环孢素A (CsA)/蒸馏水，连续14 d。取外周血、脾、骨髓。评估骨髓形态学、Notch/RBPJ kappa/FOXP3/ROR γ t信号和调节Th17/Treg平衡的分子。我们发现DNS-M能减轻小鼠AA模型的全细胞减少症。DNS-M不仅能抑制Th17细胞数量和ROR γ t的表达，还能提高Treg细胞的患病率和Foxp3的表达。此外，DNS-M可调节AA模型中Notch1、Jagged1、rbpjkappa、FOXP3、ROR γ t、DLL4的水平。这些数据表明，给药DNS-M通过调节Notch/RBPJ kappa/FOXP3/ROR γ t通路，恢复AA小鼠的Th17/Treg细胞平衡，具有治疗作用。(C) 2020作者。由Elsevier B.V.代表沙特国王大学出版。
T cell differentiation is a key pathological process of aplastic anemia (AA). Tregs and Th17 must be balanced for efficient immune tolerance. Discorea nipponica saponins (DNS) improves the recovery from hematopoiesis in AA models through its ability to increase the number of T-helper cells whilst decreasing the percentage of T-cytotoxic cells in AA mice. However, the mechanisms by which DNS leads to these therapeutic effects remains largely undefined. Here, we explored the mechanism(s) by which DNS regulates T cell subsets in mouse AA models. BALB/c male mice were used to establish the AA model using Cs-137 irradiation and intraperitoneal injection with cyclophosphamides and Chloramphenicol. Mice were administrated DNS/Tripterygium wilfordii polyglycoside tablets (TW)/cyclosporine A (CsA)/distilled water via gavage each day for 14 days. Peripheral blood, spleen and bone marrow were obtained. Bone marrow morphology, Notch/RBPJ kappa/FOXP3/ROR gamma t signaling and molecules regulating Th17/Treg balance were evaluated. We found that DNS-M attenuated pancytopenia in mouse AA models. DNS-M could not only suppressed Th17 cell numbers and ROR gamma t expression, but enhanced the prevalence of Treg cells and Foxp3 expression. Moreover, DNS-M modulated the level of Notch1, Jagged1, RBPJ kappa, FOXP3, ROR gamma t, DLL4 in AA models. These data suggest that the administration of DNS-M exhibits therapeutic effects through restoring the Th17/Treg cell balance in AA mice through its regulation of the Notch/RBPJ kappa/FOXP3/ROR gamma t pathway. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.